16-1788835-C-G

Variant names:

• chr16-1788835-C-G
• rs1065656
• NM_012225.4:c.*121C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284502.2(NUBP2):​c.491C>G​(p.Pro164Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,286,368 control chromosomes in the GnomAD database, including 303,674 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37770 hom., cov: 34)
  • Exomes 𝑓: 0.68 (265904 hom.)
• Consequence: NUBP2 NM_001284502.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 50 publications found

Genes affected

NUBP2 (HGNC:8042): (NUBP iron-sulfur cluster assembly factor 2, cytosolic) This gene encodes an adenosine triphosphate (ATP) and metal-binding protein that is required for the assembly of cyotosolic iron-sulfur proteins. The encoded protein functions in a heterotetramer with nucleotide-binding protein 1 (NUBP1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2013]

SPSB3 (HGNC:30629): (splA/ryanodine receptor domain and SOCS box containing 3) Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284502.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP2	NM_012225.4	MANE Select	c.*121C>G		3_prime_UTR	Exon 7 of 7	NP_036357.1	Q9Y5Y2
	NUBP2	NM_001284502.2		c.491C>G	p.Pro164Arg	missense	Exon 6 of 6	NP_001271431.1
	NUBP2	NM_001284501.2		c.*121C>G		3_prime_UTR	Exon 8 of 8	NP_001271430.1	H3BQR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUBP2	ENST00000262302.14	TSL:1 MANE Select	c.*121C>G		3_prime_UTR	Exon 7 of 7	ENSP00000262302.9	Q9Y5Y2
	NUBP2	ENST00000881954.1		c.*121C>G		3_prime_UTR	Exon 7 of 7	ENSP00000552013.1
	NUBP2	ENST00000942968.1		c.*121C>G		3_prime_UTR	Exon 5 of 5	ENSP00000613027.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106667 AN: 152022 Hom.: 37741 Cov.: 34

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.714

GnomAD4 exome AF: 0.682 AC: 773558 AN: 1134228 Hom.: 265904 Cov.: 15 AF XY: 0.678 AC XY: 375219 AN XY: 553424

African (AFR) AF: 0.787 AC: 19649 AN: 24966

American (AMR) AF: 0.708 AC: 13616 AN: 19230

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 12989 AN: 17846

East Asian (EAS) AF: 0.485 AC: 16096 AN: 33162

South Asian (SAS) AF: 0.564 AC: 31968 AN: 56646

European-Finnish (FIN) AF: 0.579 AC: 17604 AN: 30390

Middle Eastern (MID) AF: 0.702 AC: 2633 AN: 3752

European-Non Finnish (NFE) AF: 0.696 AC: 625852 AN: 899820

Other (OTH) AF: 0.685 AC: 33151 AN: 48416

GnomAD4 genome AF: 0.702 AC: 106748 AN: 152140 Hom.: 37770 Cov.: 34 AF XY: 0.692 AC XY: 51498 AN XY: 74372

African (AFR) AF: 0.781 AC: 32419 AN: 41530

American (AMR) AF: 0.699 AC: 10702 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2566 AN: 3472

East Asian (EAS) AF: 0.562 AC: 2895 AN: 5152

South Asian (SAS) AF: 0.584 AC: 2817 AN: 4822

European-Finnish (FIN) AF: 0.563 AC: 5965 AN: 10604

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46904 AN: 67940

Other (OTH) AF: 0.716 AC: 1513 AN: 2112

Alfa AF: 0.579 Hom.: 1532

Bravo AF: 0.722

Asia WGS AF: 0.574 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.44
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1065656; hg19: chr16-1838836; COSMIC: COSV107230274; COSMIC: COSV107230274;